Gleevec (imatinib mesylate), marketed by Novartis, is an oral medication approved by the U.S. Food and Drug Administration (FDA) for treating certain types of cancer, such as leukemia and gastrointestinal stromal tumors (GISTs).
Gleevec also is being investigated in preclinical studies as a potential treatment for amyotrophic lateral sclerosis (ALS).
How Gleevec works
Gleevec is a tyrosine kinase inhibitor (TKI). Tyrosine kinases are enzymes that activate other proteins by transferring a phosphate group to the protein. This activation is part of a signaling cascade that cancer cells need to grow and multiply. By inhibiting specific tyrosine kinases, Gleevec reduces the growth and proliferation of certain cancer cells.
In ALS patients who have a mutation in the superoxide dismutase (SOD1) gene, SOD1 protein accumulates inside cells and causes damage to motor neurons (nerve cells) that control muscle movement. It has been shown that Gleevec can reduce the levels of faulty SOD1 protein, but it is not understood how Gleevec’s function of inhibiting tyrosine kinases leads to this reduction.
Gleevec in preclinical studies
A study tested four different tyrosine kinase inhibitors, Gleevec, Sprycel (dasatinib), Bosulif (bosutinib), and Tasigna (nilotinib), on mouse cells with a SOD1 mutation. Gleevec, but none of the other three compounds, reduced the amount of faulty SOD1 protein that the cells produced.
The researchers then tested Gleevec in an ALS mouse model with the same mutation. Twelve to 14 mice received a daily dose of 2.5 mg per kg of body weight of Gleevec, starting at age 60 days, which is approximately 30 days before symptoms are expected to arise. Gleevec treatment significantly delayed the onset of symptoms, slowed disease progression, and extended the life span of the mice.
The dosage of 2.5 mg/kg corresponds to a dose of 188 mg for an adult weighing 75 kg. For cancer treatment, Gleevec is used at a similar dose range of 200-800 mg per day.
The safety profile of Gleevec in humans is known through its use as a cancer treatment. However, clinical trials are necessary to investigate whether ALS patients with a SOD1 mutation can benefit from Gleevec, and which dose is most effective.
Gleevec can cause side effects, such as bleeding problems, blurred vision, dizziness, headaches, irregular heartbeat, seizures, and mood changes.
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